Experimental Research
The circulation of antibiotic-resistant strains of Vibrio cholerae in the world requires dynamic monitoring.
The aim of the study was to assess the level of sensitivity/resistance of V. cholerae to representatives of quinolones (including fluoroquinolones) and beta-lactams.
Material and methods. The serial dilution method was used to determine the minimum inhibitory concentrations (MICs) of nalidic acid, ciprofloxacin, ampicillin, and ceftriaxone for 682 strains of V. cholerae isolated in Russia in 2005–2020 from humans and environmental objects.
Results. All toxigenic strains and 20.4 % of non-toxigenic strains were resistant to nalidixic acid; 30 to 50 % of toxigenic strains and 5.4 % of non-toxigenic strains were resistant to ceftriaxone. No resistance to imipenem was detected. In the presence of resistance genes to fluoroquinolones and beta-lactams, about half of the cultures were characterized by sensitivity to these antibiotics in vitro. Consequently, there is a risk of the emergence of antibiotic-resistant forms of the cholera pathogen during the process of etiotropic therapy of the infection, which dictates the need to monitor the sensitivity/resistance of vibrios to fluoroquinolones or beta-lactams during treatment with these antibiotics.
Introduction. The viral disease COVID-19 has caused a global emergency and attracted the attention of health professionals and the public worldwide. The significant increase in the number of new cases of infection with this virus demonstrates the relevance of finding medications effective against this pathogen. A laboratory model is needed to assess the activity of antiviral drugs.
The aim of this study was to develop an experimental model that adequately reproduces the leading syndrome of the human disease COVID-19.
Material and methods. Research methods: experimental and analytical. The experiments were conducted using a permanent culture of African green monkey kidney cells — Vero Cl008, as well as Syrian golden hamsters orally infected with various variants of the SARS-CoV-2 virus.
Results. A model of the experimental form of COVID-19 in Syrian golden hamsters with oral infection was developed based on a set of parameters (clinical, virological, hematological, and biochemical). It was shown that as a result of oral infection at a dose of 500 ID50 animals developed lung damage, a decrease in the number of leukocytes in the blood, an increase in the proportion of young and band forms of neutrophils with a simultaneous decrease in the proportion of segmented neutrophils, lymphocytes, an increase in the activity of aspartate and alanine aminotransferases (AST and ALT), an increase in the concentration of urea, creatinine, lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) in the blood serum. The following indicators were used to calculate the disease severity index and the therapeutic effect factor: virus accumulation in the lungs, the degree of lung damage (pathological changes), the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine kinase, urea, creatinine, the relative number of myelocytes, young, band, segmented neutrophils, and lymphocytes.
Conclusion. The proposed model of the experimental form of COVID-19 in Syrian golden hamsters adequately reproduces the leading syndrome of the disease (viral pneumonia) and allows for a more objective assessment of the effectiveness of antiviral drugs with the calculation of the disease severity index and the therapeutic effect coefficient.
GUIDELINES FOR PRACTITIONERS
Background. The effectiveness of treatment for multidrug-resistant (MDR)/pre-extensively drug-resistant (pre-XDR) TB directly depends on the tolerability of chemotherapy, including linezolid, a group A drug.
Aim: To study the incidence and types of adverse drug reactions (ADRs) to linezolid and ways to improve them in adolescents with MDR/pre-XDR TB.
Methods. A retrospective study included 38 patients aged 13–17 years with various forms of pulmonary TB: MDR TB — 52.6 %, pre-XDR TB — 42.1 %, XDR TB — 5.3 %. The levels of eosinophils, hemoglobin, erythrocytes, leukocytes; ALT, AST were assessed. The immunological study (lymphocyte blast-transformation reaction) was performed to evaluate linezolid tolerability. ADRs were assessed by type (allergic, toxic, toxicoallergic) and severity.
Results. The development of ADRs to linezolid was registered in 34.2 % of cases with prevailing toxic reactions (76.9 %). The most frequent reaction was anemia (46.2 %), ADRs of severity levels 1–2 were registered in 80 % of cases. ADRs were immunologically confirmed in 30.8 % of thecases — in patients with allergic, as well as both toxic and allergic reactions. In 84.6% of cases, short-term withdrawal of linezolid and symptomatic treatment were required.
Conclusion. Despite the high frequency of ADRs induced by linezolid administration, most of them were mild and could be corrected without long-term drug withdrawal.
Background. Elevated expression of TUBB3 protein is associated with resistance to taxanes and vinca alkaloids, as well as with increased metastatic potential of tumor cells. However, studies evaluating TUBB3 expression across various tumor types, including non-small cell lung cancer (NSCLC), and its association with clinically significant disease characteristics have produced inconsistent results.
The aim of the study. To assess the prognostic value of TUBB3 expression levels in NSCLC tissue as a molecular marker of disease aggressiveness.
Material and methods. An analysis was conducted on overall survival in NSCLC patients (N = 120) with varying levels of TUBB3 expression in tumor tissue, assessed using an immunofluorescence method coupled with flow cytometry. Primary monoclonal antibodies against TUBB3 (EP1569Y) and secondary antibodies conjugated with DyLight650 dye were used. Fluorescence was measured on a Navios flow cytometer, and the number of stained cells was determined using the Kolmogorov–Smirnov method in FlowJo 10.0.8 software. Statistical analysis was performed using GraphPad Prism 6.0.
Results. 1. TUBB3 expression was detected in 100 % of the analyzed NSCLC samples, with a median expression level of 40 %. 2. A reduction in patient survival and a 1.5-fold increase in hazard ratio (HR) were observed in the group with TUBB3 expression ≥ 40 % compared to < 40 %. 3. The greatest decrease in survival and the highest increase in HR (2.7- and 2.6-fold, respectively) were noted when the cutoff level for comparison was raised to ≥ 50 % versus < 50 %. 4. The greatest improvement in survival and a 1.9-fold reduction in HR were observed when the cutoff level was lowered to < 35 % versus ≥ 35 %.
Conclusion. The level of expression of the molecular marker TUBB3, which reflects the metastatic potential of tumor cells, serves as a prognostic factor for the aggressiveness of NSCLC. TUBB3 expression level ≥ 50 % can be considered a reliable molecular indicator of aggressive disease course, while a level < 35 % is a reliable marker of a more favorable prognosis.
Background. It is well known that patients with uterine cancer (UC) experience disturbances in adaptation processes during the surgical stage of treatment, which are especially pronounced in the perioperative period. These phenomena have almost never been studied, but they exist and require the use of therapeutic agents capable of influencing the systemic adaptive-regulatory control mechanisms involved in the pathological process. Such agents include the metabolic drug Remaxol®, one of the possible mechanisms of which is the formation of adaptive homeostasis by increasing the pool of general non-specific adaptive reactions (GNAR) of the physiological type.
The aim of the study was to determine the effect of Remaxol® on the possibility of forming adaptive reactions and correcting adaptive homeostasis in patients with UC in the perioperative period.
Material and methods. The prospective study included 72 patients with verified UC, aged 56–72 years. All patients were comparable by age, extent of the process, anthropometry, and were randomly distributed into the main
(N = 39) and control groups (N = 33). In the main group, Remaxol® (inosine + meglumine + methionine + nicotinamide + succinic acid) was included in therapeutic support in order to compensate for regulatory-adaptive mechanisms. It was administered intraoperatively and during the first 4 days of the perioperative period. Remaxol® was not prescribed in the control group. The structure and type of GNAR characterizing the adaptation status, its systemic interrelations, the level of reactivity in quantitative terms, were identified based on the morphological composition of the blood.
Results. The main types of general adaptive reactions and their structure in UC patients were determined. An analysis of GNAR development was carried out when Remaxol® was included in the perioperative treatment program. It was shown that its use in the system of therapeutic measures reduces the impact of surgical stress in the perioperative period.
Conclusion. The use of Remaxol® promotes the sustainable development of a sufficient number of anti-stress reactions of physiological orientation, as well as high resistance with subsequent stabilization of adaptive homeostasis in UC patients in the perioperative period.
The frequency and structure of cerebral strokes among the population living in the service area of the city polyclinic were studied. The age-gender analysis showed the prevalence of elderly and old women who had suffered a cerebral stroke. Among the risk factors, the most important were: arterial hypertension, diabetes mellitus, cardiac arrhythmia. In most cases, cerebral stroke was of the ischemic type in the basin of the right middle cerebral artery.
Aim. Analysis of the economic costs of treating patients undergoing pancreaticoduodenectomy (PDE), depending on the resistance of the microflora in the bile.
Materials and methods. This retrospective study included patients over the age of 18 who underwent PDE at the Moscow Clinical Scientific Center named after A. S. Loginov from January 2019 to May 2023. The patients were divided into two groups: patients without resistant strains in bile (group 1) and patients with resistant microflora (group 2). Subsequently, an assessment of the course of the postoperative period was carried out: the frequency of surgical site infections, the duration of hospitalization, the cost of diagnosis and treatment, as well as drug provision. The statistical analysis of the data was carried out using the R 3.4.2 statistical package.
Results. The cost of laboratory diagnostics amounted to 41,895 rubles in group 1 and 56,180 rubles in group 2 (P = 0.21); 13,000 rubles for instrumental diagnostics in group 1 and 23,500 rubles in group 2 (P = 0.084); 1,500 rubles for antibacterial therapy in group 1 and 18,000 rubles in group 2 (P = 0.39); 76,011 rubles for concomitant therapy in group 1 and 113,012 rubles in group 2 (P = 0.013). Cost analysis in the groups revealed a significant difference — 157,407 rubles in group 1 versus 282,276 rubles in the group of patients with resistant flora (P = 0.1).
Conclusion. The presence of resistant flora in patients undergoing PDE significantly increases treatment costs. The main cost-increasing factors are the high rate of infectious complications, the need to use reserve antibiotics, prolonged hospitalization, and prolonged concomitant therapy. The results highlight the importance of optimizing perioperative antibiotic prophylaxis in order to reduce costs and improve treatment effectiveness.
GUIDELINES FOR PRACTITIONERS
This article analyzes the relationship between liver pathologies and breast cancer (BC). We consider the pathophysiological mechanisms underlying this relationship, including the influence of non-alcoholic fatty liver disease (NAFLD), drug-induced liver injury (DILI), and estrogen metabolism disorders. Particular attention is paid to the molecular pathways that contribute to the development of BC against the background of liver pathologies. An overview of modern therapeutic and preventive strategies for women with identified liver pathologies, as well as for women with liver pathologies and the first signs of BC is presented. The article describes drugs with confirmed efficacy based on international studies, and also provides recommendations on diet and regimen that help improve the prognosis of survival.
REVIEWS
In recent years, an increase in the incidence of mycobacteriosis was observed. Diagnosis of mycobacteriosis remains extremely difficult, primarily due to the similarity of the clinical and radiological picture with that of tuberculosis. Cultivation of mycobacteria requires an individual approach depending on the type of mycobacteria and the conditions of their cultivation. Coverage and implementation of cultivation methods contribute to increasing the efficiency of diagnosis and treatment of diseases caused by mycobacteria. The prevalence of mycobacteriosis, which today represents a serious problem for both clinicians and laboratory specialists, requires the development of a new strategy for their microbiological diagnostics, allowing for rapid detection of drug resistance, identification of non-tuberculous mycobacteria, and the prescription of an adequate chemotherapy regimen, as well as increasing the effectiveness of treatment and preventing the spread of drug-resistant strains of mycobacteria.
Gramicidin S is a cyclic decapeptide antibiotic produced by the soil bacterium Aneurinibacillus migulanus (formerly Bacillus brevis, Brevibacillus brevis), one of the first antibiotics ever discovered. In recent years, a revival of research interest was observed towards gramicidin S due to its unique properties: it does not cause the development of antibiotic resistance and has high efficacy against biofilms. This review examines current understanding of the structure, biological role, and antimicrobial mechanisms of gramicidin S. It also explores the biosynthetic pathways of gramicidin S, as well as the influence of cultivation parameters and nutrient medium components on its biosynthesis.
Blood culture–negative endocarditis (BCNE) is an important clinical problem, since the identification of the pathogen and its sensitivity to anti-infective drugs is crucial to ensure optimal treatment of this disease. The most common causes of BCNE are the administration of antibiotics before blood culture for examination or infection with microorganisms that require special techniques and special equipment to identify them. Recognizing the extreme urgency of this problem, the American Heart Association issued a special statement, with a number of key achievements in the field of molecular diagnostics introduced into practice in recent years, as well as a variety of imaging techniques that help identify cardiac and extracardiac lesions as the leading source of motivation. This article comments on the main provisions of this document.